The incretin hormone glucagon-like peptide-1 (GLP-1) is inactivated by the enzyme dipeptidyl peptidase-4 even before it leaves the gut, but it seems to act predominantly via activation of intestinal sensory neurons expressing GLP-1 receptors. Thus, activation of vagal afferents is probably responsible for its effects on appetite and food intake, gastrointestinal secretion and motility, and pancreatic endocrine secretion. However, GLP-1 receptors are widely expressed in the gastrointestinal (GI) tract, including epithelial cells in the stomach, and the Brunner glands, in endocrine cells of the gut epithelium, and on mucosal lymphocytes. In this way, GLP-1 may have important local actions of epithelial protection and endocrine signalling and may interact with the immune system. We review the formation and release of GLP-1 from the endocrine L cells and its fate after release and describe the localization of its receptor throughout the GI tract and discuss its direct or indirect actions in the GI tract. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.
© 2021 The British Pharmacological Society.